1. Field of the Invention
The present invention relates to the use of force fields to enhance the absorption of a chemotherapeutic agent, comprising one or more particular drugs, by targeted cells and, more particularly, the use of high-frequency force fields for this purpose.
2. Description of the Prior Art
As known in the art for some time, standard chemotherapy as a treatment for a tumor or cancer, AIDS or certain other diseases involves the use of a drug (or drugs) to which particular target cells are significantly more sensitive than are normal cells. For instance, in the case of a tumor or cancer, such drugs are more effective in poisoning tumor cells than they are in poisoning normal cells, and in the case of Graves disease radioactive iodine is targeted to thyroid cells for the purpose of destroying some of them. While in some cases the chemotherapeutic drug may be applied directly to the cells of the tumor or other targeted cells themselves, usually such a drug is applied systemically. Standard chemotherapy maintains the concentration of systemically-applied drugs in the blood and other exta-cellular body fluids at a relatively low level in order to limit any damage to normal cells. However, this results in the maximum amount of the chemotherapeutic drug that is actually taken up and delivered into a targeted cell by passing through its cell plasma membrane also being limited to a lower level than would otherwise be optimum.
Recently, a new electrochemotherapy [ECT] antitumor treatment has been developed, which treatment consists of locally delivering shocks of high-intensity DC electrical pulses to tumor sites a short time after the systemic administration of chemotherapy. The DC electrical pulses open large transient pores in the plasma membranes of the exposed cells. The chemotherapeutic agents can enter the cells through these pores resulting in locally enhanced cytotoxicity. More specifically, it is believed that each high-intensity electrical DC pulse shock produces a sufficiently high force field across the plasma membrane of each of the exposed cells to cause the plasma membrane to break down and puncture in response thereto, thereby creating the aforesaid pores in the exposed cells.
ECT using DC pulses has been successfully used in conjunction with bleomycin, a cytotoxic compound which causes DNA breaks and cleaves some RNA. A few hundred bleomycin molecules in the cell cytosol are sufficient to induce cell death. In vitro experiments have shown that using 10% cell survival as a criterion, cells subjected to ECT are 650,000 times more sensitive to bleomycin than those exposed to bleomycin alone. In the case of mice with spontaneous breast tumors, the amount of bleomycin required for remission was so small that the drug if given alone was ineffective and did not seem to induce any secondary effects. Highly encouraging trial results were obtained in patients with head and neck tumors using 4 or 8 DC pulses with amplitudes of 1300 volts/cm and duration of 100 microseconds (.mu.s). The pulses were delivered by means of metallic electrodes placed on the skin on either side of the malignant nodules.
A problem is that the implementation of ECT with shocks of DC pulses and non-invasive electrodes is limited to the treatment of small cutaneous tumor lesions, since it would be very difficult to non-invasively produce the required DC electric force field strength in subcutaneous or deep-seated tumors. The present invention is directed to a solution of this problem which permits the required strength of a force field to be conveniently produced even in the cells of deep-seated tumors or other types of targeted cells using one or more non-invasive applicators.